Abstract
The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism’s contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood was processed on whole genome microarrays. Gene expression was compared between HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls. Functional analysis identified canonical pathways and molecular functions associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive LVAS patients, there were 155 genes differentially expressed compared to risk allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated the risk allele-positive and risk allele-negative LVAS patients on a principal component analysis. Pathways associated with HDAC9 risk allele-positive status involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These preliminary data suggest an association with the HDAC9 rs2107595 risk allele and peripheral immune, lipid, and clotting systems in LVAS. Further study is required to evaluate whether these differences are related to large vessel atherosclerosis and stroke risk.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-7 |
| Number of pages | 7 |
| Journal | Translational Stroke Research |
| DOIs | |
| State | Accepted/In press - Apr 13 2018 |
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Keywords
- Atherosclerosis
- Gene expression
- Ischemic stroke
- Large vessel stroke
- Polymorphism
- SNP
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel Atherosclerotic Stroke. / Shroff, Natasha; Ander, Bradley; Zhan, Xinhua; Stamova, Boryana; Liu, Da; Hull, Heather; Hamade, Farah R.; Dykstra-Aiello, Cheryl; Ng, Kwan; Sharp, Frank R; Jickling, Glen C.
In: Translational Stroke Research, 13.04.2018, p. 1-7.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel Atherosclerotic Stroke
AU - Shroff, Natasha
AU - Ander, Bradley
AU - Zhan, Xinhua
AU - Stamova, Boryana
AU - Liu, Da
AU - Hull, Heather
AU - Hamade, Farah R.
AU - Dykstra-Aiello, Cheryl
AU - Ng, Kwan
AU - Sharp, Frank R
AU - Jickling, Glen C.
PY - 2018/4/13
Y1 - 2018/4/13
N2 - The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism’s contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood was processed on whole genome microarrays. Gene expression was compared between HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls. Functional analysis identified canonical pathways and molecular functions associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive LVAS patients, there were 155 genes differentially expressed compared to risk allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated the risk allele-positive and risk allele-negative LVAS patients on a principal component analysis. Pathways associated with HDAC9 risk allele-positive status involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These preliminary data suggest an association with the HDAC9 rs2107595 risk allele and peripheral immune, lipid, and clotting systems in LVAS. Further study is required to evaluate whether these differences are related to large vessel atherosclerosis and stroke risk.
AB - The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism’s contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood was processed on whole genome microarrays. Gene expression was compared between HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls. Functional analysis identified canonical pathways and molecular functions associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive LVAS patients, there were 155 genes differentially expressed compared to risk allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated the risk allele-positive and risk allele-negative LVAS patients on a principal component analysis. Pathways associated with HDAC9 risk allele-positive status involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These preliminary data suggest an association with the HDAC9 rs2107595 risk allele and peripheral immune, lipid, and clotting systems in LVAS. Further study is required to evaluate whether these differences are related to large vessel atherosclerosis and stroke risk.
KW - Atherosclerosis
KW - Gene expression
KW - Ischemic stroke
KW - Large vessel stroke
KW - Polymorphism
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=85045283642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85045283642&partnerID=8YFLogxK
U2 - 10.1007/s12975-018-0619-x
DO - 10.1007/s12975-018-0619-x
M3 - Article
C2 - 29651704
AN - SCOPUS:85045283642
SP - 1
EP - 7
JO - Translational Stroke Research
JF - Translational Stroke Research
SN - 1868-4483
ER -